- MD, University of Heidelberg, Germany
- PhD, University of Heidelberg, Germany
- BS, American University of Beirut, Lebanon
- Associate Professor, Microbiology, Immunology, and Cancer Biology
- Phone: 982-6634
- Email: email@example.com
Basic and tanslational brain tumor research
Our research focuses on understanding the molecular basis of brain tumor and glioblastoma development and growth and on using the acquired knowledge to identify new therapeutic targets and develop new therapeutic approaches. Specifically, the following projects are ongoing in the lab at this time:
1. MicroRNAs in brain tumors: We are studying the expressions, mechanisms of action and functions of several microRNAs that are predicted to target or mediate the effects of important oncogenic molecules in brain tumors. We are also using novel global microRNA target screening approaches (PAR-CLIP and CLASH) to uncover the compendium of microRNA targets in brain tumors. The ultimate goal is to understand the role of microRNAs in brain tumor development and growth and to identify master regulatory microRNAs that can be used or targeted for therapy with novel molecular delivery approaches.
2. MET and other receptor tyrosine kinases (RTK) in brain tumors: We previously established the MET pathway as a contributor to brain tumor malignancy. Clinically applicable inhibitors of MET have been subsequently developed but have thus far failed to achieve significant effects in human patients. We hypothesized that this failure is due to signaling redundancy and compensatory mechanisms involving various other pathways and molecules including other RTKs. Our goal is to understand how MET interacts with these pathways and molecules, and to use this understanding to develop new therapies that target MET in combination with other molecules. We are also interested in uncovering the determinants of sensitivity and resistance to MET inhibitors in order to better select patients that will benefit for MET inhibition and to develop new approaches for overcoming resistance to anti-MET drugs.
3. Novel interactions between the tumor suppressor PTEN and mutant p53: 3. Novel interactions between the tumor suppressor PTEN and mutant p53: We discovered that the tumor suppressor PTEN can exhibit unexpected tumor-promoting properties. We have evidence that these tumor-promoting properties of PTEN are due to its interactions with gain-of-function mutant p53. We are systematically studying these, previously unknown, interactions between PTEN and mutant-p53 and their implications for prognosis and the design of anti-tumor therapies. The findings will provide new mechanistic insights into the interactions between PTEN and p53 mutants in human cancer, have prognostic value and determine the settings and pre-conditions under which manipulating tumor suppressor expression and function can lead to successful anti-tumor therapies.
4. T type calcium channels in glioblastoma stem cells: We recently developed interest in studying the molecular mechanisms and targeting for glioblastoma therapy of T type calcium channels. The goal is to understand their role in cancer stem cells and to develop channel blockers as novel adjuvants for the clinical therapy of glioblastoma.
- Li Y, Lal B, Kwon S, Fan X, Saldanha U, Reznik T, Kuchner E, Eberhart C, Laterra J, Abounader R. The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy. Cancer research. 2005;65(20): 9355-62. PMID: 16230398
- Li Y, Guessous F, Johnson E, Eberhart C, Li X, Shu Q, Fan S, Lal B, Laterra J, Schiff D, Abounader R. Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in large-cell medulloblastoma. Laboratory investigation; a journal of technical methods and pathology. 2007;88(2): 98-111. PMID: 18059365
- Li Y, Guessous F, Kwon S, Kumar M, Ibidapo O, Fuller L, Johnson E, Lal B, Hussaini I, Bao Y, Laterra J, Schiff D, Abounader R. PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations. Cancer research. 2008;68(6): 1723-31. PMID: 18339852
- Li Y, Guessous F, Kwon S, Kumar M, Ibidapo O, Fuller L, Johnson E, Lal B, Hussaini I, Bao Y, Laterra J, Schiff D, Abounader R. PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations. Cancer Res. 2008;68(6): 1723-31. PMCID: NIHMS135586
- Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen T, Lopes B, Schiff D, Purow B, Abounader R. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer research. 2009;69(19): 7569-76. PMID: 19773441 | PMCID: PMC2756313
- Li Y, Guessous F, DiPierro C, Zhang Y, Mudrick T, Fuller L, Johnson E, Marcinkiewicz L, Engelhardt M, Kefas B, Schiff D, Kim J, Abounader R. Interactions between PTEN and the c-Met pathway in glioblastoma and implications for therapy. Molecular cancer therapeutics. 2009;8(2): 376-85. PMID: 19190120
- Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, Purow B, Abounader R. microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell cycle (Georgetown, Tex.). 2010;9(6): 1031-6. PMID: 20190569 | PMCID: PMC3278213
- Guessous F, Yang Y, Johnson E, Marcinkiewicz L, Smith M, Zhang Y, Kofman A, Schiff D, Christensen J, Abounader R. Cooperation between c-Met and focal adhesion kinase family members in medulloblastoma and implications for therapy. Molecular cancer therapeutics. 2011;11(2): 288-97. PMID: 22188814 | PMCID: PMC3277676
- Guessous F, Alvarado-Velez M, Marcinkiewicz L, Zhang Y, Kim J, Heister S, Kefas B, Godlewski J, Schiff D, Purow B, Abounader R. Oncogenic effects of miR-10b in glioblastoma stem cells. Journal of neuro-oncology. 2013;112(2): 153-63. PMID: 23307328
- Huang X, Zhang Y, Tang Y, Butler N, Kim J, Guessous F, Schiff D, Mandell J, Abounader R. A novel PTEN/mutant p53/c-Myc/Bcl-XL axis mediates context-dependent oncogenic effects of PTEN with implications for cancer prognosis and therapy. Neoplasia (New York, N.Y.). 2013;15(8): 952-65. PMID: 23908595
- Zhang Y, Farenholtz K, Yang Y, Guessous F, Dipierro C, Calvert V, Deng J, Schiff D, Xin W, Lee J, Purow B, Christensen J, Petricoin E, Abounader R. Hepatocyte growth factor sensitizes brain tumors to c-MET kinase inhibition. Clinical cancer research : an official journal of the American Association for Cancer Research. 2013;19(6): 1433-44. PMID: 23386689
- Kofman A, Kim J, Park S, Dupart E, Letson C, Bao Y, Ding K, Chen Q, Schiff D, Larner J, Abounader R. microRNA-34a promotes DNA damage and mitotic catastrophe. Cell cycle (Georgetown, Tex.). 2013;12(22): 3500-11. PMID: 24091633
- Kim J, Zhang Y, Skalski M, Hayes J, Kefas B, Schiff D, Purow B, Parsons S, Lawler S, Abounader R. microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma. Cancer research. 2014. PMID: 24425048